Safety and reactogenicity of BCG revaccination with isoniazid pretreatment in TST positive adults

Abstract

Rationale: Global tuberculosis (TB) control may require mass vaccination with a new TB vaccine, such as a recombinant bacille Calmette Guerin (BCG) or attenuated Mycobacterium tuberculosis (MTB). The safety profile of live mycobacterial vaccines in latently infected adults with prior infant BCG vaccination is unknown.

Objectives: Evaluate safety and reactogenicity of BCG revaccination, with or without isoniazid (INH) pretreatment, in adults with latent MTB infection (LTBI).

Methods: Eighty-two healthy, HIV uninfected, South African adults, with a BCG scar and tuberculin skin test (TST) diameter ≥ 15 mm, were randomized to receive 6 months of INH, starting either before, or 6 months after, intradermal revaccination with BCG Vaccine SSI (Statens Serum Institut, Copenhagen). Safety and reactogenicity data are reported through 3 months post BCG revaccination.

Results: Baseline characteristics were similar between treatment arms. Mean baseline TST diameter was 20 ± 4 mm. Seventy-two subjects received BCG revaccination. Injection site erythema (68%) and induration (86%) peaked 1 week after revaccination. Ulceration (76%) peaked at 2 weeks, and resolved by 3 months in all but 3 subjects. Diameter of ulceration was >10mm in only 8%, but a residual scar was common (85%). No regional lymphadenitis or serious morbidity related to BCG was seen. Reactogenicity was not affected by INH pretreatment.

Conclusion: BCG revaccination of MTB infected adults is safe, well tolerated, and reactogenicity is similar to that of primary BCG vaccination. Clinical trials of live recombinant BCG or attenuated MTB vaccines may be considered in latently infected adults, with or without INH pretreatment (ClinicalTrials.gov identifier: NCT01119521).

Keywords: BCG; Isoniazid; LTBI; Revaccination; Safety.

Copyright © 2014 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Participant Flow

Figure 2

(a – c) Evolution and resolution of local reactogenicity (erythema, induration, and ulceration) over three months following BCG revaccination in the INH arm and observation arm respectively. Error bars are interquartile range, minimum-maximum range, with median line and outliers.

Figure 2

(a – c) Evolution and resolution of local reactogenicity (erythema, induration, and ulceration) over three months following BCG revaccination in the INH arm and observation arm respectively. Error bars are interquartile range, minimum-maximum range, with median line and outliers.